Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer
Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer
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DOI：
10.1016/j.bbrc.2009.05.048
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发表时间：
2009-07-31
影响因子：
3.1
通讯作者：
Lo, Wen-Liang
中科院分区：
文献类型：
--
作者：
Chen, Yu-Chih;Chen, Yi-Wei;Lo, Wen-Liang
醛脱氢酶1（ALDH 1）被认为是癌症干细胞的标志物。然而，ALDH 1在头颈部鳞状细胞癌（HNSCC）中的作用尚未确定。在这项研究中，我们从HNSCC患者中分离出ALDH 1阳性细胞，并表明这些HNSCC-ALDH 1（+）细胞显示出放射抗性，并代表了产生肿瘤的储库。基于芯片结果，Western印迹和免疫荧光检测的结果进一步证实了ALDH 1（+）-谱系细胞显示出具有上皮-间充质转化（EMT）移位和内源性共表达Snail的证据。此外，Snail表达的敲低显著降低了ALDH 1的表达，抑制了癌干细胞样性质，并阻断了CD 44（+）CD 24（-）ALDH 1（+）细胞的致瘤能力。最后，在异种移植致瘤性研究中，我们证实了Snail siRNA可以提高ALDH 1（+）放化疗的治疗效果。总之，ALDH 1可能是HNSCC的癌干细胞样细胞的特异性标志物。(C)2009 Elsevier Inc. All rights reserved.
Aldehyde dehydrogenase 1 (ALDH1) has been considered to be a marker for cancer stern cells. However, the role of ALDH1 in head and neck squamous cell carcinoma (HNSCC) has yet to be determined. In this study, we isolated ALDH1-positive cells from HNSCC patients and showed that these HNSCC-ALDH1(+) cells displayed radioresistance and represented a reservoir for generating tumors. Based on microarray findings, the results of Western blotting and immunofluorescent assays further confirmed that ALDH1(+)-line-age cells showed evidence of having epithelial-mesenchymal transition (EMT) shifting and endogenously co-expressed Snail. Furthermore, the knockdown of Snail expression significantly decreased the expression of ALDH1, inhibited cancer stern-like properties, and blocked the tumorigenic abilities of CD44(+)CD24(-)ALDH1(+) cells. Finally, in a xenotransplanted tumorigenicity study, we confirmed that the treatment effect of chemoradiotherapy for ALDH1(+) could be improved by Snail siRNA. In summary, it is likely that ALDH1 is a specific marker for the cancer stern-like cells of HNSCC. (C) 2009 Elsevier Inc. All rights reserved.